Antifungals Flashcards
what layer do superficial, subcutaneous, and systemic mycoses affect
superficial: outermost layers of skin, nails, hair, mucous membranes
subcutaneous: dermis, subcutaneous tissue, and adjacent bone
systemic - internal organs
antifungals that affect cell membrane permeability
polyenes - amphotericin B and nyostatin
azoles: ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, clotrimazole, miconazole
allylamines - terbinafine
antifungal that blocks nucleic acid synthesis
flucytosine
antifungal that disrupts microtubule function
Griseofulvin
antifungal that disrupts the fungal cell wall
echinocandins: caspofungin
what are the antifungal systemic drugs for subcutaneous and systemic mycoses
Flucytosine
Azoles: PFVIK – posaconazole, fluconazole, voriconazole, itraconazole, ketoconazole
Polyenes: amphotericin B
Echinocandins: Caspofungin
what are the systemic antifungals for superficial mycoses
GAA
Griseofulvin
Allylamines: Terbinafine
Azoles: FIK – fluconazole, itraconazole, ketoconazole
what are the topical antifungals for superficial mycoses
Polyenes: amphotericin B and Nystatin
Allylamines: Terbinafine
Azoles: CMK – clotrimazole, miconazole, ketoconazole
mechanism of amphoTEARricin B
bind to ergosterol and TEARS a hole/form pores in cell membrane –> leakage of intracellular ions and macromolecules –> cell death
drug of use for deep fungal infections during pregnancy
amphotericin B
what phase is amphotericin B used in and why?
it is usually used in the induction phase to rapidly reduce fungal burden then replaced with an azole for chronic use
conditions amphotericin B commonly used in
mucormycosis, cryptococcal meningitis, histoplasmosis, blastomycosis, coccidiodomycosis, extracutaneous sporotrichosis, fusariosis, and other systemic fungal infections
what is usually given before treatment of amphotericin B
saline solution to keep the electrolytes balanced
common adverse effects of amphotericin B
RENAL TOXICITY due to amphotericin B binding to cholesterol in mammalian cell membrane and forming pores
magnesium and potassium wasting hence why saline is given
what steps have been taken to reduce nephrotoxicity with amphotericin B
formulation of lipid amphotericin B such as
Liposomal Amphotericin B (L-AMB)
Amphotericin B Lipid Complex (ABLC)
Amphotericin B Colloid Complex (ABCC)
they all decrease drug exposure to proximal tubule of the nephron
mechanism of flucystosine
converted to 5-fluorouracil –> 5 fluorodeoxyuridine –> inhibits thymidylate sythetase –> blocks synthesis of
fluorouridine triphosphate also formed –> blocks protein synthesis
what two antifungals are usually used synergistically in the induction phase
amphotericin B and flucystosine
what are amphotericin B and flucytosine used synergistically to treat
Candida and Cryptococcus
adverse effects of flucytosine
due to toxic fluorouracil –>
Bone marrow toxicity with anemia
Leukopenia
Thrombocytopenia
BLT
what are the imidazoles
Clotrimazole
Miconazole
Ketoconazole
what are the triazoles
F VIP Fluconazole Voriconazole Itraconazole Posaconazole
mechanism of the azoles
inhibits CYP450 enzyme 14α-sterol demethylase which converts lanesterol to ergosterol which is needed for cell membrane of the fungus
what interferes with absorption of ketoconazole
antacids, H2 blocker, PPI –> since they all increased pH
ketoconazole absorbed best at low pH
adverse effects of ketoconazole
decreases testosterone –> gynecomastia
inhibits adrenal steroid synthesis –> decreases plasma cortisol conc
what condition is fluconazole used in especially if amphotericin B is not available
cryptococcus meningitis
effective against aspergillus
Voriconazole
adverse effect of Voriconazole
visual disturbances including blurring and changes in color vision or brightness
effective against Zygomycetes such as Mucor
Posaconazole
what antifungal drugs is an echinocandins and what is its mechanism
Caspofungin –> inhibits synthesis of β(1-3)-D-glucans in the fungal cell wall –> disruption of fungal cell wall –> cell death
use of Griseofulvin
only used for treatment of dermatophytosis - skin, hair, nails
mechanism of Griseofulvin
interacts with microtubules of fungus to disrupt mitotic spindle and inhibit mitosis
Griseofulvin has been replaced with what antifungals
Itraconazole and Terbinafine
adverse of Griseofulvin
induces liver P450 enzymes –> increasing metabolism of warfarin
mechanism of terbinafine
inhibits squalene epoxidase which turn squalene to lanesterol which is need to turn to ergosterol for fungal cell membrane
mechanism of nystatin
structurally similar to amphotericin B and has same mechanism where it makes pores in the cell membrane –> leaky –> cell death
what is nystatin used only to treat and what is adverse effect
candidiasis
bitter taste in mouth
two azoles most commonly used topically
clotrimazole and miconazole
what type of microorganism is pneumocystis jirovecii
now recognized as a fungus but responds to antiprotozoals and not antifungals
first line therapy for treatment of pneumocystis pneumonia
TMP-SMX (trimethoprim-sulfamethoxazole) aka co-trimoxazole
what other medication can be given in combination with TMP-SMX and for what reason
corticosteroid preferably prednisone if P02 is less than 70
alternative therapies for PCP
Clindamycin + Primaquine
Dapsone + Trimethoprim
Atovaquone
Pentamidine
CP DAP
